Agtrap

Type-1 angiotensin II receptor-associated protein (AT1 receptor-associated protein)

Spatial tier: REGION_BIASED · Class: GPCR · Top region: SCO (Subcommissural organ) · Positive regions: 43/554

42.0Discovery Score
39.1Targetability Score
CEvidence grade C
What this means: Agtrap: fine CCF profile is region-biased toward SCO (top regions: SCO, OV, MEPO, ME, LM); this is a discovery lead, not direct proof.

Function in SCO: evidence, prediction, innovation

Gene function
AGTRAP (ATRAP) is a three-transmembrane intracellular protein that binds the carboxy-terminal tail of the angiotensin II type 1 receptor and promotes its constitutive internalisation, acting as a brake on AT1R signalling. It also interacts with other membrane proteins, including transferrin receptor 1 and the cardiac calcium pump SERCA2a, so it behaves as a general trafficking adaptor.
Region function
The subcommissural organ is an ependymal secretory gland in the roof of the third ventricle at the posterior commissure; it secretes SCO-spondin into cerebrospinal fluid to form Reissner's fibre, which contributes to CSF flow, aqueduct patency and axial/neurodevelopmental signalling.
Published in this region
inferred No region-specific literature found. The closest brain evidence is from another periventricular/hypothalamic site: Sotozawa 2024 showed that enhancing ATRAP in the paraventricular hypothalamic nucleus suppresses angiotensin II-dependent hypertension by limiting AT1R signalling and sympathetic outflow.
Predicted function
Prediction: in subcommissural organ ependymocytes ATRAP would set how strongly these cells respond to CSF and blood-borne angiotensin II by controlling AT1R surface density, tuning secretion of SCO-spondin and local fluid handling in the aqueduct. Over-expressing Agtrap in SCO should dampen angiotensin-evoked calcium signalling and secretion, while knockdown should sensitise the organ to angiotensin, predicted to alter Reissner's fibre output and CSF flow; a hypertension-linked readout (angiotensin-driven drinking or sympathetic tone) is the natural behavioural test.
Innovation
★★★★★ 5/5 Angiotensin signalling in the subcommissural organ, and its adaptor-level regulation, has never been examined even though the organ faces the CSF where angiotensin acts.
Tools
Agtrap knockout and tissue-specific transgenic mice; anti-ATRAP antibodies; AT1R antagonists (losartan, candesartan) as pathway context; FoxJ1-CreER and ICV AAV for ependymal targeting.
References

Direct evidence located at the region

Agtrap Allen ISH at the CCF centroid of SCO

Allen ISH experiment 69028581, section image 68867655 (section 158): the section that contains the CCF centroid of Subcommissural organ according to the Allen image-to-atlas alignment (reference_to_image), with a 2 mm window around that point. Left: whole section, red box = window. Middle: ISH signal. Right: Allen's expression-mask view of the same window. open this image in the Allen viewer

Direct spatial evidence

MERFISH REGION LOCATOR
SCO MERFISH region locator
Real single-cell MERFISH coordinates for the SCO (Subcommissural organ) section -- our own ground-truth data, showing exactly where this region sits, independent of whether the Allen ISH section below is easy to read.

Regional expression figure

Agtrap regional expression profile

Predicted WMB × fine-CCF profile; not direct full-transcriptome spatial measurement.

Spatial profile

SCO
2.49
OV
2.05
MEPO
2.02
ME
1.92
LM
1.86
AP
1.84
MMd
1.72
PVp
1.68
AVPV
1.66
SFO
1.58
NLOT1
1.54
ENTl1
1.51
AD
1.5
PVi
1.5
RT
1.47
PVpo
1.39
SCzo
1.39
VMPO
1.38
AUDd1
1.36
V
1.35

Evidence and specificity

Evidence status
PREDICTED_FINE
Direct sources
None; predicted localization only
Exclusive threshold
12 positive regions out of 554
Spatial specificity
0.280
Top-region fraction
0.042
Filter status
PASS

Interpretation limits